• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

一个远端的 Foxp3 增强子使依赖白细胞介素 2 的胸腺 Treg 细胞谱系承诺产生强大的免疫耐受。

A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance.

机构信息

Howard Hughes Medical Institute and Immunology Program, Ludwig Center at Memorial Sloan Kettering Cancer Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10021, USA.

Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

出版信息

Immunity. 2021 May 11;54(5):931-946.e11. doi: 10.1016/j.immuni.2021.03.020. Epub 2021 Apr 9.

DOI:10.1016/j.immuni.2021.03.020
PMID:33838102
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8317508/
Abstract

Activation of the STAT5 transcription factor downstream of the Interleukin-2 receptor (IL-2R) induces expression of Foxp3, a critical step in the differentiation of regulatory T (Treg) cells. Due to the pleiotropic effects of IL-2R signaling, it is unclear how STAT5 acts directly on the Foxp3 locus to promote its expression. Here, we report that IL-2 - STAT5 signaling converged on an enhancer (CNS0) during Foxp3 induction. CNS0 facilitated the IL-2 dependent CD25Foxp3 precursor to Treg cell transition in the thymus. Its deficiency resulted in impaired Treg cell generation in neonates, which was partially mitigated with age. While the thymic Treg cell paucity caused by CNS0 deficiency did not result in autoimmunity on its own, it exacerbated autoimmune manifestations caused by disruption of the Aire gene. Thus, CNS0 enhancer activity ensures robust Treg cell differentiation early in postnatal life and cooperatively with other tolerance mechanisms minimizes autoimmunity.

摘要

白细胞介素-2 受体 (IL-2R) 下游的 STAT5 转录因子的激活诱导 Foxp3 的表达，这是调节性 T (Treg) 细胞分化的关键步骤。由于 IL-2R 信号的多效性，STAT5 如何直接作用于 Foxp3 基因座以促进其表达尚不清楚。在这里，我们报告说，IL-2-STAT5 信号在 Foxp3 诱导过程中集中在一个增强子 (CNS0) 上。CNS0 促进了 IL-2 依赖性 CD25Foxp3 前体细胞向胸腺中 Treg 细胞的转化。其缺乏导致新生儿 Treg 细胞生成受损，随着年龄的增长而部分缓解。虽然 CNS0 缺陷引起的胸腺 Treg 细胞缺乏本身不会导致自身免疫，但它会加剧 Aire 基因破坏引起的自身免疫表现。因此，CNS0 增强子活性确保了出生后早期 Treg 细胞的分化，并与其他耐受机制合作，最大限度地减少自身免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/179e9c316842/nihms-1699834-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/0fc7c1f7f18e/nihms-1699834-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/9790f8cdc392/nihms-1699834-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/c0260a2ee440/nihms-1699834-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/9dd305ed2e04/nihms-1699834-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/7d4d6fc395dc/nihms-1699834-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/878b81fbb441/nihms-1699834-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/179e9c316842/nihms-1699834-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/0fc7c1f7f18e/nihms-1699834-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/9790f8cdc392/nihms-1699834-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/c0260a2ee440/nihms-1699834-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/9dd305ed2e04/nihms-1699834-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/7d4d6fc395dc/nihms-1699834-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/878b81fbb441/nihms-1699834-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/8317508/179e9c316842/nihms-1699834-f0007.jpg

相似文献

1
A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance.一个远端的 Foxp3 增强子使依赖白细胞介素 2 的胸腺 Treg 细胞谱系承诺产生强大的免疫耐受。
Immunity. 2021 May 11;54(5):931-946.e11. doi: 10.1016/j.immuni.2021.03.020. Epub 2021 Apr 9.
2
Distinct Foxp3 enhancer elements coordinate development, maintenance, and function of regulatory T cells.不同的 Foxp3 增强子元件协调调节性 T 细胞的发育、维持和功能。
Immunity. 2021 May 11;54(5):947-961.e8. doi: 10.1016/j.immuni.2021.04.005. Epub 2021 Apr 29.
3
The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation.调节性 T 细胞的谱系稳定性和抑制性程序需要蛋白质 O-GlcNAcylation。
Nat Commun. 2019 Jan 21;10(1):354. doi: 10.1038/s41467-019-08300-3.
4
The adaptor TRAF3 restrains the lineage determination of thymic regulatory T cells by modulating signaling via the receptor for IL-2.衔接蛋白 TRAF3 通过调节 IL-2 受体信号来抑制胸腺调节性 T 细胞的谱系确定。
Nat Immunol. 2014 Sep;15(9):866-74. doi: 10.1038/ni.2944. Epub 2014 Jul 20.
5
Upregulation of Foxp3 expression in mouse and human Treg is IL-2/STAT5 dependent: implications for the NOD STAT5B mutation in diabetes pathogenesis.小鼠和人类调节性T细胞中Foxp3表达的上调依赖于白细胞介素-2/信号转导子和转录激活子5：对糖尿病发病机制中NOD信号转导子和转录激活子5B突变的影响
Ann N Y Acad Sci. 2006 Oct;1079:198-204. doi: 10.1196/annals.1375.031.
6
IL-2Rbeta links IL-2R signaling with Foxp3 expression.白细胞介素-2受体β链将白细胞介素-2受体信号传导与叉头框蛋白3表达联系起来。
Eur J Immunol. 2007 Jul;37(7):1817-26. doi: 10.1002/eji.200737101.
7
Requirement for POH1 in differentiation and maintenance of regulatory T cells.POH1 在调节性 T 细胞分化和维持中的需求。
Cell Death Differ. 2019 Mar;26(4):751-762. doi: 10.1038/s41418-018-0162-z. Epub 2018 Jul 23.
8
Interleukin 2 modulates thymic-derived regulatory T cell epigenetic landscape.白细胞介素 2 调节胸腺来源的调节性 T 细胞表观遗传景观。
Nat Commun. 2018 Dec 18;9(1):5368. doi: 10.1038/s41467-018-07806-6.
9
STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+CD25- effector T cells.信号转导及转录激活因子5（STAT5）信号细胞因子调节CD4+CD25+调节性T细胞和CD4+CD25-效应T细胞中FOXP3的表达。
Int Immunol. 2008 Mar;20(3):421-31. doi: 10.1093/intimm/dxn002. Epub 2008 Feb 12.
10
IL-2 family of cytokines in T regulatory cell development and homeostasis.白细胞介素-2细胞因子家族在调节性T细胞发育及内环境稳定中的作用
J Clin Immunol. 2008 Nov;28(6):635-9. doi: 10.1007/s10875-008-9235-y. Epub 2008 Aug 26.

引用本文的文献

1
Asymmetry and redundancy of STAT5 paralogs across CD8 T cell differentiation states.STAT5旁系同源物在CD8 T细胞分化状态间的不对称性和冗余性。
bioRxiv. 2025 Jul 28:2025.07.23.666302. doi: 10.1101/2025.07.23.666302.
2
Interferon Regulatory Factor 4 dose-dependently controls peripheral Treg cell differentiation and homeostasis by modulating chromatin accessibility in mice.干扰素调节因子4通过调节小鼠的染色质可及性，以剂量依赖的方式控制外周调节性T细胞的分化和稳态。
Front Immunol. 2025 Jul 14;16:1604888. doi: 10.3389/fimmu.2025.1604888. eCollection 2025.
3
Immunosuppressive mechanisms and therapeutic targeting of regulatory T cells in ovarian cancer.

本文引用的文献

1
Regulatory T Cells and Human Disease.调节性 T 细胞与人类疾病。
Annu Rev Immunol. 2020 Apr 26;38:541-566. doi: 10.1146/annurev-immunol-042718-041717. Epub 2020 Feb 4.
2
Dynamic Imprinting of the Treg Cell-Specific Epigenetic Signature in Developing Thymic Regulatory T Cells.在胸腺调节性 T 细胞发育过程中动态印迹 Treg 细胞特异性表观遗传特征。
Front Immunol. 2019 Oct 11;10:2382. doi: 10.3389/fimmu.2019.02382. eCollection 2019.
3
Hidden Caveat of Inducible Cre Recombinase.诱导型Cre重组酶的潜在隐患
卵巢癌中调节性T细胞的免疫抑制机制及治疗靶点
Front Immunol. 2025 Jul 9;16:1631226. doi: 10.3389/fimmu.2025.1631226. eCollection 2025.
4
Characterization of peripheral immune cells in kidney transplantation recipients under different immunosuppressive treatments.不同免疫抑制治疗下肾移植受者外周免疫细胞的特征分析
Front Immunol. 2025 Jun 11;16:1605664. doi: 10.3389/fimmu.2025.1605664. eCollection 2025.
5
The role of Treg cells in colorectal cancer and the immunotherapy targeting Treg cells.调节性T细胞在结直肠癌中的作用及针对调节性T细胞的免疫治疗
Front Immunol. 2025 Apr 16;16:1574327. doi: 10.3389/fimmu.2025.1574327. eCollection 2025.
6
STAT Signature Dish: Serving Immunity with a Side of Dietary Control.STAT特色菜品：提供免疫力并辅以饮食控制。
Biomolecules. 2025 Mar 26;15(4):487. doi: 10.3390/biom15040487.
7
Exploring molecular and cellular mechanisms of Pre-Metastatic niche in renal cell carcinoma.探索肾细胞癌中前转移微环境的分子和细胞机制。
Mol Cancer. 2025 Apr 22;24(1):121. doi: 10.1186/s12943-025-02315-9.
8
Genome-wide CRISPR screen in human T cells reveals regulators of FOXP3.人类T细胞中的全基因组CRISPR筛选揭示了FOXP3的调控因子。
Nature. 2025 Mar 26. doi: 10.1038/s41586-025-08795-5.
9
The TET-TDG axis in T cells and biological processes.T细胞中的TET-TDG轴与生物学过程。
Int Immunol. 2025 May 21;37(6):299-312. doi: 10.1093/intimm/dxaf006.
10
Elusive modes of Foxp3 activity in versatile regulatory T cells.多功能调节性T细胞中难以捉摸的Foxp3活性模式。
Front Immunol. 2025 Jan 15;15:1533823. doi: 10.3389/fimmu.2024.1533823. eCollection 2024.
Immunity. 2019 Oct 15;51(4):591-592. doi: 10.1016/j.immuni.2019.09.010.
4
IL-2 production by self-reactive CD4 thymocytes scales regulatory T cell generation in the thymus.自身反应性 CD4 胸腺细胞产生的白细胞介素 2 调节了胸腺中调节性 T 细胞的生成。
J Exp Med. 2019 Nov 4;216(11):2466-2478. doi: 10.1084/jem.20190993. Epub 2019 Aug 21.
5
An Nfil3-Zeb2-Id2 pathway imposes Irf8 enhancer switching during cDC1 development.Nfil3-Zeb2-Id2 通路在 cDC1 发育过程中诱导 Irf8 增强子切换。
Nat Immunol. 2019 Sep;20(9):1174-1185. doi: 10.1038/s41590-019-0449-3. Epub 2019 Aug 12.
6
Essential and non-overlapping IL-2Rα-dependent processes for thymic development and peripheral homeostasis of regulatory T cells.调控性 T 细胞的胸腺发育和外周组织稳态所必需且不重叠的 IL-2Rα 依赖性过程。
Nat Commun. 2019 Mar 4;10(1):1037. doi: 10.1038/s41467-019-08960-1.
7
Thymic regulatory T cells arise via two distinct developmental programs.胸腺调节性 T 细胞通过两个不同的发育程序产生。
Nat Immunol. 2019 Feb;20(2):195-205. doi: 10.1038/s41590-018-0289-6. Epub 2019 Jan 14.
8
Differential Roles of IL-2 Signaling in Developing versus Mature Tregs.IL-2 信号在 Treg 细胞发育和成熟中的差异作用
Cell Rep. 2018 Oct 30;25(5):1204-1213.e4. doi: 10.1016/j.celrep.2018.10.002.
9
A timer for analyzing temporally dynamic changes in transcription during differentiation in vivo.用于分析体内分化过程中转录的时间动态变化的定时器。
J Cell Biol. 2018 Aug 6;217(8):2931-2950. doi: 10.1083/jcb.201711048. Epub 2018 Jun 25.
10
Extrathymically Generated Regulatory T Cells Establish a Niche for Intestinal Border-Dwelling Bacteria and Affect Physiologic Metabolite Balance.胸腺外生成的调节性 T 细胞为肠道边界寄居菌建立了小生境，并影响生理代谢物平衡。
Immunity. 2018 Jun 19;48(6):1245-1257.e9. doi: 10.1016/j.immuni.2018.04.013. Epub 2018 May 29.